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Research from Monell, Integral Molecular Displays Bitterness Inhibition

Posted: June 3, 2011

Scientists from the Monell Center and Integral Molecular discovered a compound that inhibits bitterness by acting directly on a subset of bitter taste receptors.

Bitterness is detected by a family of approximately 25 different taste receptors called TAS2Rs. Together, the TAS2Rs respond to an array of structurally different compounds, many of which are found in nature and can be toxic.

Discovery of bitter blockers would help scientists understand the signaling mechanisms of these receptors and promote the design of novel and more effective blockers. “Bitter taste is a major problem for pediatric drug compliance and also for proper nutrition, such as eating those healthy but bitter green vegetables,” said Monell senior author Paul Breslin, a sensory biologist. “But we currently have very limited ways to effectively control bitter taste.”

Monell and Integral Molecular are currently collaborating on a project to understand the structure and function of TAS2Rs, and in a serendipitous discovery, researchers found probenecid, a molecule used in receptor assays, is an inhibitor of a subset of bitter taste receptors. The study, published in PLoS ONE, showed a series of in vitro studies revealing probenecid does not physically block interaction of bitter molecules with the receptor’s primary binding site. Rather, it appears to bind elsewhere on the receptor to modulate the receptor’s ability to interact with the bitter molecule.

“Probenecid’s mechanism of action makes it a useful tool for understanding how bitter receptors function,” said Integral Molecular senior author Joseph B. Rucker. “This knowledge will help us develop more potent bitter taste inhibitors.”